The proposed work is directed toward the goal of determining what role is played by nonspecific carboxylesterases and specific and nonspecific carboxylamidases in the mechanisms of cellular growth control and oncogenic transformation. An initial goal is the completion of the synthesis of a series of fluorogenic protease substrates that should permit the development of assays that are 100 to 1000 times more sensitive than conventional synthetic substrate assays for proteolytic enzymes. These assays will be used to determine the levels of the various enzyme activities in subcellular fractions from normal and transformed cells under various growth conditions. The total nonspecific carboxylesterase activity in soluble fractions from normal and transformed cells has been shown to be the result of the combined action of a substantial number of individual enzymes in every case examined so far. The effect of oncogenic transformation and of various changes in growth conditions on the profiles of enzyme activity in gel electrophoresis is being investigated. A program to isolate variant cell lines that lack individual isozymes of the nonspecific carboxylesterases will be initiated in the near future.